The illusive promise of circumcision to prevent female-to-male HIV infection – not the way to go for South Africa

‘Circumcision reduces HIV infections 76% in South Africa, researchers find’,
screamed the headline in the online Bloomberg news, taking its cue from
the reported findings of a randomised, controlled intervention trial
(RCT) conducted at Orange Farm, Gauteng. The findings were presented by
French researcher Bertran Auvert et al.
in July 2011 at an AIDS conference in Rome, showing that circumcision
significantly reduced the risk of female-to-male transmission of HIV.
‘We are changing the social norm,’ Auvert gushed at a news
conference. ‘It’s the first time in the world that we have
a successful intervention in a community to reduce the sexual
transmission of HIV between adults.’

University of the Witwatersrand researcher Francois Venter echoed the triumphant tone, telling the Bulletin of the WHO
that ‘Male circumcision is the most powerful intervention we have
at this point in time. One of [its] beauties is that it is a one-off
operation which takes 15 - 20 minutes but then has a profound effect on
the rest of a man’s life; whereas to promote condom use or
microbicides, repeated long-term promotion is needed.’ The most
powerful intervention? A lay listener might be forgiven for concluding
that circumcision represents a silver bullet that renders conventional
prevention strategies obsolete.

Indeed, Marwick Khumalo, a Member of Parliament in Swaziland, was
quoted in the local press as saying: ‘All male children should be
circumcised. To show my seriousness, I have taken all my sons for
circumcision.’ The KwaZulu-Natal correctional services report a
near-stampede by prison inmates across the province demanding to be
circumcised, and the authorities are scurrying about to set up
circumcision stations in the prisons from their limited HIV prevention
resources, apparently oblivious to the absence of any evidence that
circumcision prevents male-to-male HIV transmission.

The evidence

The Orange Farm study was one of three independent RCTs conducted in South Africa,1 Uganda2 and Kenya3
to determine whether circumcision reduced the risk of female-to-male
transfer of HIV infection during penetrative heterosexual sex. The
results showed that the intervention significantly reduced the
incidence of HIV infection in the circumcised study group compared with
the controls, by 60% in South Africa, 53% in Kenya and 51% in Uganda.
In all three studies, the benefits of intervention observed on interim
calculations were judged by the researchers to be sufficiently
convincing to justify early termination of the RCTs on ethical grounds.

The published conclusion of the South African study is more
circumspect, declaring simply that ‘Male circumcision provides a
degree of protection against acquiring HIV infection, equivalent to
what a vaccine of high efficacy would have achieved. Male circumcision
may provide an important way of reducing the spread of HIV infection in
sub-Saharan Africa.’ The comparison to a vaccine has been
contested, but the constrained demeanour is probably closer to reality.

The extended claim that circumcision confers lifelong protection
seems like a stretch, and cannot be inferred from this or the other
RCTs, all of which were terminated at 24 months or less. And because
the control group were also offered circumcision at the termination of
the RCT, the opportunity to continue longer-term follow-up was forever
extinguished.

The three RCTs sought to test what has long been suggested in many
epidemiological studies, dating back to 1987, that enquired into
circumcision as a risk factor for HIV-1 infection among men. The
studies, though not always consistent, appeared to show that
circumcision reduces the risk of HIV infection in men. They were
conducted in a wide variety of populations and environments, and a
large diversity of research conditions. In 2000, Weiss et al.4
published a systematic review and meta-analysis of such studies, and
concluded that ‘Male circumcision is associated with a
significantly reduced risk of HIV infection among men in sub-Saharan
Africa, particularly those at high risk of HIV.’ However, the
authors concede that meta-analyses are vulnerable to bias because
studies yielding statistically significant findings are more likely to
be submitted and published than studies with negative results.

On the other hand, a much-cited Cochrane systematic review from the
South African Medical Research Council (MRC) published three years
later,5 while also finding
‘a strong epidemiological association between male circumcision
and prevention of HIV, especially among high-risk groups’,
nevertheless cautioned that there was ‘insufficient evidence to
support an interventional effect of male circumcision on HIV
acquisition in heterosexual men’ because ‘the observational
studies are inherently limited by confounding which is unlikely to be
fully adjusted for’.

That was before the three RCTs, publication of which has led to the
current drive to inflict mass circumcision on southern African men.
Circumcision intervention has now been embraced by the WHO, the Centers
for Disease Control, other health-based organisations and some
researchers. Even the MRC has since reversed its position, with lead
researcher Siegfried declaring on 15 April 2009 that ‘Research on
the effectiveness of male circumcision for preventing HIV in
heterosexual men is conclusive. No further trials are required to
establish that HIV infection rates are reduced in heterosexual men for
at least the first two years after circumcision.’

However, the three RCTs have not been without detractors. In a scathing critique, Van Howe and Storms6
point out that ‘In the South African trial, men who reported at
least one episode of unprotected sex accounted for 2 498 person-years
and 46 HIV infections during the trial. Among the remaining men, who
accounted for 2076 person-years, 23 became infected although they
either had no sexual contact or always used a condom …
Similarly, in the Ugandan trial, men who consistently used condoms had
the same rate of infection as those who never used condoms. Finally, in
the first three months of the Kenyan trial, five men became
HIV-positive who reported no sexual activity in the period before the
seroconversion.’ They conclude from their recalculations and
statistical reasoning that ‘Conservatively for the three trials,
89 of the 205 infections (43.1%) were sexually transmitted. Without
knowing which infections were sexually transmitted [and which were
not], it is impossible to test the hypothesis of whether circumcision
reduces the rate of sexually transmitted HIV.’ Such studies, it
must be said, depend on subject self-reporting, and, sexuality being a
very private matter, the subjects may sometimes be inclined to be less
than candid.

Protagonists have touted universal neonatal circumcision (proscribed
in South Africa under current law) even though, as cogently argued by
Sidler et al.,7
no credible evidence exists linking circumcision to future protection
from HIV in adulthood. The scale of the projected implementation is
staggering. Kelly Curran, Technical Director of the HIV/AIDS and
Infectious Diseases Department affiliated with Johns Hopkins University,8
envisages a roll-out aimed at 80% coverage in 13 countries involving
approximately 28 million (that’s right, 28 million) procedures
over 5 years. In Zambia and Swaziland, a partnership has been launched
to circumcise 642 000 adolescent boys and men over 5 years, with
the support of a start-up grant of $50 million from the Bill and
Melinda Gates Foundation. It is curious and even worrisome that the
campaign to circumcise African men seems to be driven by donor funding
and researchers from the North.

Why rolling out circumcision is not the way to go for South Africa

For all the drum-beating promotion of
universal circumcision prophylaxis in southern Africa, the big question
remains: what man would want to accept circumcision and the associated
risks, if he were made clearly to understand the need to continue to
abstain, be faithful and/or condomise? What then would be the benefit?
A UNAIDS statement of 19 March 2009 states categorically that
‘The male latex condom is the single most efficient, available
technology to reduce the sexual transmission of HIV and other sexually
transmitted infections.’ Circumcision, on the other hand, is more
expensive, more invasive and less effective by itself. As Van Howe and
Storms6 put it, ‘It is
not hard to see that circumcision is either inadequate (otherwise there
would be no need for the continued use of condoms) or redundant (as
condoms provide nearly complete protection).’ Circumcision
roll-out will divert scarce resources in money, human resources and
infrastructure away from essential health services, in a system that is
already severely under-provided. Francois Venter is cited by Chris
Bateman9 as stating quite
correctly that circumcision roll-out would require
‘“serious energy, money and resources” for an
effective scale-up of what he believed should be a stand-alone
service’. In South Africa today, VCT, ART and PMTCT – all
of them with a proven impact on prevention – should merit more
priority than circumcision in resource allocation.

Several authors have pointed out as well that, without field
testing, it is impossible to predict the applicability and
repeatability of the RCT findings in real-world situations. That the
RCTs were terminated early does not help. Nor does South Africa’s
experience with the HIV epidemic offer any clues. It is true that the
Eastern Cape (EC)’s Xhosa speakers, who traditionally circumcise,
have relatively lower prevalence rates (11%) than KwaZulu-Natal’s
Zulu speakers (16%), who do not. The difference is not huge, and the EC
rates are still way too high by any standard. On the other hand, the
Western Cape, with a spotty circumcision tradition, has the lowest
prevalence (6%) in the country, almost half that of the EC (ASSA2003
Projections for 2010). According to one nationwide demographic survey,10 12.3% of circumcised men were HIV-positive, and 12.0% of intact men were similarly HIV-positive. Van Howe and Storms6
observe that among developed nations, the USA has the highest rate of
(largely neonatal) circumcision and the highest rate of heterosexually
transmitted HIV. Within the USA, black Americans have the highest rate
of circumcision and the highest rate of heterosexually transmitted HIV.
These data certainly show no distinct pattern relative to circumcision
and the risk of HIV infection.

There is a real risk that the roll-out of circumcision will dilute
the standard prevention messages and undermine the gains already made
in respect of condom use and behaviour modification. This could result
from risk compensation – a false sense of security. Risk
compensation occurs when people engage in risky behaviour in the
mistaken belief that they have acquired assured protection. For
example, in their modelling exercise, Blower and McClean11
found that if an HIV vaccine offered 50% protection, but reduced condom
use or increased other risky behaviours, it would be likely to result
in higher HIV infection rates. The enthusiasm for circumcision among
traditionally non-circumcising populations suggests that circumcision
is perceived as special and sufficient protection, and there is a risk
that medically circumcised men may feel ‘liberated’ to
engage in risky behaviour, putting themselves and their partners in
danger of infection. There is already some evidence to this effect. In
the survey by Bridges et al.12
assessing determinants of demand for circumcision, South African men
listed ‘It means that men don’t have [to] use a
condom’ as an advantage of circumcision. It is noteworthy that
circumcision does not protect women from infection risk, but may well
increase that risk in the event of risk compensation by their partner.

South Africa must take a page from the book of the Australian Federation of AIDS Organisations13
which, in rejecting circumcision for Australia, reiterated that
‘correct and consistent condom use, not circumcision, is the most
effective means of reducing female-to-male transmission, and
vice-versa. Circumcision does not prevent HIV – in high
prevalence areas it reduces the risk
of female-to-male transmission. HIV acquisition rates were nevertheless
high in both the circumcised and the non-circumcised groups involved in
the trials.’